Aim: This study was aimed to develop Eudragit S100-coated, pH-awakened microbeads (MBs) encapsulating folic acid (FA)-modified tristearin solid lipid nanoparticles (SLNs) loaded with oxaliplatin (OP). Afterward, these formulations were evaluated (in vitroandin vivo) for their potential against colorectal cancer (CRC). Methods: The SLNs were synthesised by employing the solvent diffusion technique and then they were entrapped in the MBs. The prepared uncoupled and coupled SLNs (SLN-OP and FA-SLN-OP, respectively) were examined forin vitrocytotoxicity effect against COLO-205. Gamma-scintigraphy study was used for determining biodistribution (in vivo) of drug in different organs through MBs. Results: Outcomes for FA-SLN-OP revealed more cytotoxicity (50% inhibitory concentration [IC50] = 6.8 mu g/ml) against COLO-205 cells (in vitro) than OP solution (IC50 = 8.0 mu g/ml) and SLN-OP (IC50 = 7.5 mu g/ml). MBs were also investigatedin vivousing Gamma-scintigraphy study. After 48 h study,Tc-99m-EuB-FA-SLN-OP confirmed an elevated level of drug in the colonic tumour, which was found significantly (p< 0.0001) higher than that of Tc-99m-EuB-SLN-OP. Conclusions: In conclusion, developed MBs formulation (Tc-99m-EuB-FA-SLN-OP) suggested promising results against therapy of CRC using dual targeting (i.e. ligand-directed and pH-awakened) approach.